Abstract
Recently, formaldehyde (FA), existing in a number of different cells including neural cells, was found to affect age-related cognitive impairment. Oral administration of methanol (the metabolic precursor of FA) triggers formation of senile plaques (SPs) and Tau hyperphosphorylation in the brains of monkeys with memory decline. Intraperitoneal injection of FA leads to hyperphosphorylation of Tau in wild-type mouse brains and N2a cells through activation of glycogen synthase kinase-3β (GSK-3β). Furthermore, formaldehyde at low concentrations can directly induce Tau aggregation and amyloid β (Aβ) peptide deposits in vitro. Formaldehyde-induced Tau aggregation is implicated in cytotoxicity and neural cell apoptosis. Clarifying how FA triggers Aβ deposits and Tau hyperphosphorlyation will not only improve our understanding of the molecular and cellular mechanisms of age-related cognitive impairment but will also contribute to the ongoing investigation of alternate targets for new drugs. Here, we review the role of FA, particularly that of endogenous origin, in protein aggregation and as a potential drug intervention in the development of agerelated cognitive impairment.
Keywords: Aggregation, Alzheimer’s disease, Amyloid β, Aspartame, Formaldehyde (FA), Hyperphosphorylation, Methanol, Tau protein.
Current Topics in Medicinal Chemistry
Title:Formaldehyde as a trigger for protein aggregation and potential target for mitigation of age-related, progressive cognitive impairment
Volume: 16 Issue: 5
Author(s): Tao Su, Woodrow C. Monte, Xintian Hu, Yingge He and Rongqiao He
Affiliation:
Keywords: Aggregation, Alzheimer’s disease, Amyloid β, Aspartame, Formaldehyde (FA), Hyperphosphorylation, Methanol, Tau protein.
Abstract: Recently, formaldehyde (FA), existing in a number of different cells including neural cells, was found to affect age-related cognitive impairment. Oral administration of methanol (the metabolic precursor of FA) triggers formation of senile plaques (SPs) and Tau hyperphosphorylation in the brains of monkeys with memory decline. Intraperitoneal injection of FA leads to hyperphosphorylation of Tau in wild-type mouse brains and N2a cells through activation of glycogen synthase kinase-3β (GSK-3β). Furthermore, formaldehyde at low concentrations can directly induce Tau aggregation and amyloid β (Aβ) peptide deposits in vitro. Formaldehyde-induced Tau aggregation is implicated in cytotoxicity and neural cell apoptosis. Clarifying how FA triggers Aβ deposits and Tau hyperphosphorlyation will not only improve our understanding of the molecular and cellular mechanisms of age-related cognitive impairment but will also contribute to the ongoing investigation of alternate targets for new drugs. Here, we review the role of FA, particularly that of endogenous origin, in protein aggregation and as a potential drug intervention in the development of agerelated cognitive impairment.
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Cite this article as:
Su Tao, Monte C. Woodrow, Hu Xintian, He Yingge and He Rongqiao, Formaldehyde as a trigger for protein aggregation and potential target for mitigation of age-related, progressive cognitive impairment, Current Topics in Medicinal Chemistry 2016; 16 (5) . https://dx.doi.org/10.2174/1568026615666150813142215
DOI https://dx.doi.org/10.2174/1568026615666150813142215 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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